My research effort is directed toward unraveling the relationships between mood and temporal, rhythmic changes in monoamine levels in CSF. The current project merges serotonin and depression interests from previous work at Yale with techniques in CSF sampling developed at Vanderbilt. Pilot data indicate that oscillatory patterns in monoamine metabolite levels may be more important than absolute concentrations. We are able at Vanderbilt to monitor CSF neurochemistry over 48-hour periods with q10 minute samples, to demonstrate dynamic oscillations in monoamine metabolite levels using Fourier transform methods, and to isolate dominant period lengths of these cycles. These methods are extremely promising as a hard science/engineering approach to understanding the dynamic interactions between monoamine systems that contribute to depression. The K23 Research Career Award will create dedicated time needed for my research career to become an independent researcher in this area. Although I have good psychiatric skills, my training program will require additional knowledge in applied mathematics and statistics to enable me to analyze further the neurochemical data and develop better methods for assessing oscillations in monoaminergic function. Plans for the award period include didactic courses in these areas as well as in the responsible and ethical conduct of research. The research strategy will develop under the guidance of mentors who specialize in different areas but who, together can help me produce quality research with a novel approach. My long range career goals are to honor the legacy of my mentors by bringing a new generation of researchers to the challenge and rewards of discovery, and to further the understanding of the physiologic basis of mood regulation with the aim of discovering more reliable and direct means for alleviating depression.